Abdominal aortic aneurysms are a common problem in the field of peripheral vascular surgery, and the cause of the disease is presently unknown. The presence of generalized arteriomegaly in most patients with fusiform aneurysms of the abdominal aorta suggests that there may be an underlying disorder of connective tissue that has never been recognized. There are several animal models of aneurysms; but the one most closely resembling the common fusiform aneurysm of the human abdominal aorta is the spontaneous aortic aneurysm of the Blotchy mouse (MoBlo), which causes death by rupture and not by dissection. The mutation of the Blotchy mouse is X-linked and results in a decreased tissue copper concentration and decreased lysyl oxidase (which cross-links collagen and elastin). Since the trait is X-linked, only male mice are affected. Preliminary studies have been directed towards identifying possible "markers" of the disorder in the mouse for study in human subjects. We have found elastin abnormalities and unusual smooth muscle cells in the aortic wall of young mice prior to the development of aneurysms. In addition, there is an increase in salt-soluble collagen in affected mouse skin, and also there are changes in the mechanical properties of skin. We have confirmed a decrease in hepatic copper levels in the mouse, and a preliminary retrospective study of autopsy-derived human material suggests that there may also be a decrease in human hepatic copper in patients who have died with aneurysms. The specific aims of this proposal are to complete longitudinal studies of the Blotchy mouse and to carry out a prospective study of these potential "markers" in skin biopsies taken from human subjects at the time of surgery. The significance of this proposal is that an improved understanding of aneurysms may point to a genetic basis for the disease in humans. Aortic aneurysms are a disease predominantly of males, and the X-chromosome is known to be highly conserved. In addition, it may be possible in due course to identify patients at risk for aneurysms, to develop methods for prevention, and to develop a more rational scheme than presently exists for timing the elective surgical repair of asymptomatic small aneurysms.